Although polycythenia might be expected to be a beneficial adaptation to hypoxia or altitude previous information suggests that this may not be so. Information about the hemodynamic response to polycythemia applies to a wide range of patients with both cardiovascular and pulmonary disease, but little is known about the effects and interactions of polycythemia, increased total blood volume, and hypoxia in conscious, exercising animals or humans. This proposal seeks to clarify the hemodynamic effects of polycythemia in conscious animals and to evaluate the role of hypoxia, exercise, and total blood volume, separately and combined, in these polycythemic animals. I will also study the effects of polycythemia on regional blood flow and on specific organ function. To accomplish this aim, I propose to use chronically instrumented, conscious dogs to: (1) characterize the hemodynamic effects and changes in oxygen transport at rest and during exercise with induced normovolenic polycythemia; (2) characterize the hemodynamic effects and changes in oxygen transport at rest and during exercise with induced hypervolemic polycythemia; (3) determine the mechanism of cardiac output changes in polycythemia by using red blood cells with methemoglobin todissociate the viscosity and oxygen content changes of polycythemia; (4) characterize the combined effects of hypoxia and polycythemia at rest and during exercise; (5) determine the chronic effects of induced polycythemia on total blood volume.